Subluxação atlantoaxial canina

The atlantoaxial subluxation or luxation is an instability of this articulation that produces excessive flexion of this joint causing the cranial aspect of the axis to rotate dorsally into the vertebral channel with subsequent spinal cord compression. This disorder is most commonly found in young small breed dogs. The diagnosis of this disease is done by survey radiographs, where there is a larger distance between the atlas dorsal arch and the axis spinal process characterize the atlantoaxial subluxation. Surgical stabilization is the treatment of choice and multiple implants show the best results to stabilize the atlantoaxial joint. The main complications are sudden death or implant failure. The sudden death happens because of cardiorespiratory arrest and it is most likely caused by brainstem iatrogenic trauma. However, a larger study comparing different surgical stabilization techniques should be performed to evaluate relative success rates in dogs that have the same initial neurologic status

Morte, família e a compreensão fenomenológica: revisão sistemática de literatura

The phenomenological research aims to understand how human beings mean their experiences and allows a detailed investigation of issues related to human life. In order to understand how the death experience within the family has been addressed by studies within phenomenological research perspective, a systematic review of literature was performed based on abstracts indexed in Lilacs, PEPsic, Medline e PsycInfo, by means of the intersection of the keywords: family, death, and phenomenology. Overall, 54 papers were found. Initially, all the papers were subjected to a quantitative analysis, after which 15 were selected for qualitative analysis. The results indicated that studies with grounding in phenomenology addressed three major themes: the experiences, meanings and coping with grief and loss, the family’s relationship with the terminally ill patient, and the experiences of families facing sudden death.

Relationship between sweet orange yield and intensity of Citrus Variegated Chlorosis

Citrus Variegated Chlorosis (CVC) is currently present in approximately 40% of citrus plants in Brazil and causes an annual loss of around 120 million US dollars to the Brazilian citrus industry. Despite the fact that CVC has been present in Brazil for over 20 years, a relationship between disease intensity and yield loss has not been established. In order to achieve this, an experiment was carried out in a randomized block design in a 3 x 2 factorial scheme with 10-year-old Natal sweet orange. The following treatments were applied: irrigation with 0, 50 or 100% of the evapotranspiration of the crop, combined with natural infection or artificial inoculation with Xylella fastidiosa, the causal agent of CVC. The experiment was evaluated during three seasons. A negative exponential model was fitted to the relationships between yield versus CVC severity and yield versus Area Under Disease Progress Curve (AUDPC). In addition, the relationship between yield versus CVC severity and canopy volume was fitted by a multivariate exponential model. The use of the AUDPC variable showed practical limitations when compared with the variable CVC severity. The parameter values in the relationship of yieldCVC severity were similar for all treatments unlike in the multivariate model. Consequently, the yieldCVC intensity relationship (with 432 data points) could be described by one single model: y = 114.07 exp(-0.017 x), where y is yield (symptomless fruit weight in kg) and x is disease severity (R2 = 0.45; P < 0.01).

Isolation and characterization of sodium 2-fluoroacetate from Mascagnia rigida using chromatography and infrared spectroscopy

Sodium monofluoroacetate was first identified in Dichapetalum cymosum, a South African plant that can cause livestock poisoning and death. After, several other plants also showed to contain this toxin, which leads to the "sudden death". Mascagnia rigida, a well identified poisonous plant, commonly found in northeast of Brazil also cause sudden death in cattle, which shows clinical signs similar to those produced by the ingestion of plants that contain monofluoroacetate. Our aim was to identify the toxic compound present in the aqueous extract of M. rigida. For this purpose, the dried and milled plant was extracted; the extract was lyophilized and submitted to successive chromatographic process, until the desired purity of the active compound was achieved. The study of this material by planar chromatography and by infrared spectrometry indicated that the toxin can be a mixture of mono, di and trifluoroacetate. (C) 2012 Elsevier Ltd. All rights reserved.

Bacillus cereus infection outbreak in captive psittacines

This study reports an uncommon epizootic outbreak of Bacillus cereus that caused the sudden death of 12 psittacines belonging to the species Anodorhynchus hyacinthinus (1 individual), Diopsittaca nobilis (1 individual), Ara severe (1 individual) and Ara ararauna (9 individuals) in a Brazilian zoo. Post-mortem examination of the animals reveled extensive areas of lung hemorrhage, hepatic congestion, hemorrhagic enteritis and cardiac congestion. Histopathological examination of the organs showed the presence of multiple foci of vegetative cells of Gram-positive bacilli associated with discrete and moderate mononuclear inflammatory cell infiltrate. Seventeen B. cereus strains isolated from blood and sterile organs of nine A. ararauna were analyzed in order to investigate the genetic diversity (assessed by Rep-PCR) and toxigenic profiles (presence of hblA, hblC and hblD; nheA, nheB and nheC as well as cytK, ces and entFM genes) of such strains. Amplification of genomic DNA by Rep-PCR of B. cereus strains generated two closely related profiles (Rep-PCR types A and B) with three bands of difference. All strains were classified as belonging to the toxigenic profile I which contained HBL and NHE gene complexes, entFM and cytK genes. Altogether, microbiological and histopathological findings and the evidence provided by the success of the antibiotic prophylaxis, corroborate that B. cereus was the causative agent of the infection that killed the birds. (C) 2012 Elsevier B.V. All rights reserved.

Parathyroid hormone and phosphorus overload in uremia: impact on cardiovascular system

Background. Cardiac remodeling in uremia is characterized by left ventricular hypertrophy, interstitial fibrosis and microvascular disease. Cardiovascular disease is the leading cause of death in uremic patients, but coronary events alone are not the prevalent cause, sudden death and heart failure are. We studied the cardiac remodeling in experimental uremia, evaluating the isolated effect of parathyroid hormone (PTH) and phosphorus. Methods. Wistar rats were submitted to parathyroidectomy (PTx) and 5/6 nephrectomy (Nx); they also received vehicle (V) and PTH at normal (nPTH) or high (hPTH) doses. They were fed with a poor-phosphorus (pP) or rich-phosphorus (rP) diet and were divided into the following groups: 'Sham': G1 (V + normal-phosphorus diet (np)) and 'Nx + PTx': G2 (nPTH + pP), G3 (nPTH + rP), G4 (hPTH + pP) and G5 (hPTH + rP). After 8 weeks, biochemical analysis, myocardium morphometry and arteriolar morphological analysis were performed. In addition, using immunohistochemical analysis, we evaluated angiotensin II, alpha-actin, transforming growth factor-beta (TGF-beta) and nitrotyrosine, as well as fibroblast growth factor-23 (FGF-23), fibroblast growth factor receptor-1 (FGFR-1) and runt-related transcription factor-2 (Runx-2) expression. Results. Nx animals presented higher serum creatinine levels as well as arterial hypertension. Higher PTH levels were associated with myocardial hypertrophy and fibrosis as well as a higher coronary lesion score. High PTH animals also presented a higher myocardial expression of TGF-beta, angiotensin II, FGF-23 and nitrotyrosine and a lower expression of alpha-actin. Phosphorus overload was associated with higher serum FGF-23 levels and Runx-2, as well as myocardial hypertrophy. FGFR-1 was positive in the cardiomyocytes of all groups as well as in calcified coronaries of G4 and G5 whereas Runx-2 was positive in G3, G4 and G5. Conclusion. In uremia, PTH and phosphorus overload are both independently associated with major changes related to the cardiac remodeling process, emphasizing the need for a better control of these factors in chronic kidney disease.

Cardiovascular autonomic dysfunction in sickle cell anemia

Sickle cell anemia (SCA) is associated to increased cardiac output, normal heart rate (HR), abnormal QT dispersion and lower diastolic blood pressure (DBP). The mechanisms are still unknown. The objective of this study was to test the hypothesis that there is cardiovascular autonomic dysfunction (CAD) in SCA. The secondary objectives were to distinguish the roles of chronic anemia and hemoglobinopathy and to evaluate the predominance of the sympathetic or parasympathetic systems in the pathogenesis of CAD. Sixteen subjects with SCA, 13 with sickle cell trait (SCT), 13 with iron deficiency anemia (IDA), and 13 healthy volunteers (HV) were evaluated. All subjects were submitted to 24 h-electrocardiogram (24 h-ECG), plasma norepinephrine (NE) measurement before and after isometric exercise (IE), and also Valsalva maneuver (VM), diving maneuver (DV), and tilt test (TT). Baroreflex sensitivity (BRS) was also evaluated. The minimum, average and maximum HR as well as the percentage of bradycardia and tachycardia at 24-h ECG were similar in all groups. NE at baseline and after IE did not differ between groups. The SCA group showed less bradycardia at phase IV of VM, less bradycardia during DV, and also less tachycardia and lower DBP during TT. BRS for bradycardia and tachycardia reflex was decreased in the SCA and SCT groups. In conclusion, 1) there is CAD in SCA, and it is characterized by the reduction of BRS and the limitation of HR modulation mediated by the parasympathetic system; 2) cardiovascular sympathetic activity is preserved in SCA; and 3) hemoglobinopathy is the preponderant ethiopathogenic factor. (C) 2011 Elsevier B.V. All rights reserved.

Comparison of the larynx-associated lymphoid tissue in the false vocal cords and subglottis in pediatric autopsies

The aim this work was to compare the distribution of cellular phenotypes of the LF in the FVC to the ones in the subglottic region in pediatric autopsy, relating this distribution to age and different causes of death. We analyzed 60 larynges of newborns and children autopsied in the period from 1993 to 2003. The fragments were prepared in order to perform histochemical and immunohistochemical techniques. The morphological analysis showed cases that presented LF only in FVC (35%), LF only in the subglottic region (20%), lack of LF in FVC (30%) and lymphoid aggregates, which did not characterize an LF (15%). The cases of LF in the subglottic region were significantly younger compared to the ones that presented LF in the FVC (p = 0.017). The LF in the subglottic region was bigger than the LF in the FVC (p = 0.020). There was no significant difference between the cause of death and cellular phenotype for both FVC and the subglottic region. In conclusion, the cells that make up the LF in the FVC in newborns and children younger than one year have functional characteristics similar to LF cells in the subglottic region, suggesting that there are similarities with LALT. (c) 2012 Elsevier GmbH. All rights reserved.

A comparison between diuretics and angiotensin-receptor blocker agents in patients with stage I hypertension (PREVER-treatment trial): study protocol for a randomized double-blind controlled trial

Abstract Background Cardiovascular disease is the leading cause of death in Brazil, and hypertension is its major risk factor. The benefit of its drug treatment to prevent major cardiovascular events was consistently demonstrated. Angiotensin-receptor blockers (ARB) have been the preferential drugs in the management of hypertension worldwide, despite the absence of any consistent evidence of advantage over older agents, and the concern that they may be associated with lower renal protection and risk for cancer. Diuretics are as efficacious as other agents, are well tolerated, have longer duration of action and low cost, but have been scarcely compared with ARBs. A study comparing diuretic and ARB is therefore warranted. Methods/design This is a randomized, double-blind, clinical trial, comparing the association of chlorthalidone and amiloride with losartan as first drug option in patients aged 30 to 70 years, with stage I hypertension. The primary outcomes will be variation of blood pressure by time, adverse events and development or worsening of microalbuminuria and of left ventricular hypertrophy in the EKG. The secondary outcomes will be fatal or non-fatal cardiovascular events: myocardial infarction, stroke, heart failure, evidence of new subclinical atherosclerosis and sudden death. The study will last 18 months. The sample size will be of 1200 participants for group in order to confer enough power to test for all primary outcomes. The project was approved by the Ethics committee of each participating institution. Discussion The putative pleiotropic effects of ARB agents, particularly renal protection, have been disputed, and they have been scarcely compared with diuretics in large clinical trials, despite that they have been at least as efficacious as newer agents in managing hypertension. Even if the null hypothesis is not rejected, the information will be useful for health care policy to treat hypertension in Brazil. Clinical trials registration number ClinicalTrials.gov: NCT00971165

Ectomycorrhizae of sessile oak (Quercus petraea (Matt.) Liebl.)

Investigations were performed during the years 1999 to 2001 on a limed and unlimed plot within a high-elevated sessile oak forest. The oak forest (with 90 years old European beech at the understorey) was 170 to 197 years old. It is located at forest district Merzalben, location 04/0705, which is situated in the Palatinate Forest in south-west Germany. Liming was performed in December 1988 when 6 tons/ha of powdered Dolomite were brought up by the forestry department. Liming was performed to counteract the effects of soil acidification (pH(H2O) at Horizon A (0-10 cm): 3.9), which is induced by long-term (anthropogenic) acidic cloud cover and precipitation. Potentially toxic Al3+ ions, which become solubilized below pH 5, were suspected to be responsible for forest dieback and sudden death of the mature oaks. The most logical entry point for these toxic ions was suspected to occur in the highly absorptive region of the ectomycorrhizae (fungal covered root tips). However, the diversity and abundance of oak-ectomycorrhizal species and their actual roles in aluminum translocation (or blockage) were unknown. It was hypothesized that the ectomycorrhizae of sessile oaks in a limed forest would exhibit greater seasonal diversity and abundance with less evidence of incorporated aluminum than similar oak ectomycorrhizae from unlimed soils. To test this hypothesis, 12 oaks in the limed plot and 12 in an adjacent unlimed plot were selected. Each spring and fall for 2 years (1999 & 2000), 2 sets of soil cylinders (9.9 cm dia.) were extracted from Horizon A (0-10 cm), Horizon B (30-40 cm) and Horizon C (50-60 cm depth) at a distance of 1 meter from each tree base. Roots were extracted from each probe by gentle sieving and rinsing. Soil samples were retained for pH (H2O, CaCl2, and KCl) and moisture analysis. One set of roots was sorted by size and air-dried for biomass analysis. The finest mycorrhizal roots of this set were used for bound and unbound (cytosolic) mineral [Al, Ca, Mg, K, Na, Mn, S, Zn, Fe, Cd and Pb] analysis (by Landwirtschaftliche Untersuchungs- und Forschungsanstalt Rheinland Palatinate (LUFA)). Within 7 days of collection, the mycorrhizal tips from the second set of probes were excised, sorted, identified (using Agerer’s Color Atlas), counted and weighed. Seasonal diversity and abundance was characterized for 50 of the 93 isolates. The location and relative abundance of Al within the fungal and root cell walls was characterized for 68 species using 0.01% Morin dye and fluorescence microscopy. Morin complexes with Al to produce an intense yellow fluorescence. The 4 most common species (Cenococcum geophilum, Quercirhiza fibulocsytidiata, Lactarius subdulcis, Piceirhiza chordata) were prepared for bound Al, Ca, Fe and K mineral analysis by LUFA. The unlimed and limed plots were then compared. Only 46 of the 93 isolated ectomycorrhizal species had been previously associated with oaks in the literature. Mycorrhizal biomass was most abundant in Horizon A, declining with depth, drought and progressive soil acidification. Mycorrhizae were most diverse (32 species) in the limed plot, but individual species abundance was low (R Selection) in comparison to the unlimed plot, where there were fewer species (24) but each species present was abundant (K Selection). Liming increased diversity and altered dominance hierarchy, seasonal distributions and succession trends of ectomycorrhizae at all depths. Despite an expected reduction in Al content, the limed ectomycorrhizae both qualitatively (fluorescence analysis) and quantitatively (mineral analysis) contained more bound Al, especially so in Horizon A. The Al content qualitatively and quantitatively increased with depth in the unlimed and limed plots. The bound Al content fluctuated between 4000-and 20000 ppm while the unbound component was consistently lower (4 -14 ppm). The relative amount of unbound Al declined upon liming implying less availability for translocation to the crown area of the trees. This correspouds with the findings of good crown appearance and lower tree mortality in the limed zone. Each ectomycorrhizal species was unique in its ability to block, sequester (hold) or translocate Aluminum. In several species, Al uptake varied with changes in moisture, pH, depth and liming. According to the fluorescence study, about 48% of the isolated ectomycorrhizal species blocked and/or sequestered (held) Al in their mantle and/or Hartig net walls, qualitatively lowering bound Al in the adjacent root cell walls. Generally, if Al was more concentrated in the fungal walls, it was less evident in the cortex and xylem and conversely, if Al was low or absent from the fungal walls it was frequently more evident in the cortex and xylem.

The effects of hypocalcemia on spatial alternans and ventricular fibrillation studied with the optical mapping technique

The heart is a wonderful but complex organ: it uses electrochemical mechanisms in order to produce mechanical energy to pump the blood throughout the body and allow the life of humans and animals. This organ can be subject to several diseases and sudden cardiac death (SCD) is the most catastrophic manifestation of these diseases, responsible for the death of a large number of people throughout the world. It is estimated that 325000 Americans annually die for SCD. SCD most commonly occurs as a result of reentrant tachyarrhythmias (ventricular tachycardia (VT) and ventricular fibrillation (VF)) and the identification of those patients at higher risk for the development of SCD has been a difficult clinical challenge. Nowadays, a particular electrocardiogram (ECG) abnormality, “T-wave alternans” (TWA), is considered a precursor of lethal cardiac arrhythmias and sudden death, a sensitive indicator of risk for SCD. TWA is defined as a beat-to-beat alternation in the shape, amplitude, or timing of the T-wave on the ECG, indicative of the underlying repolarization of cardiac cells [5]. In other words TWA is the macroscopic effect of subcellular and celluar mechanisms involving ionic kinetics and the consequent depolarization and repolarization of the myocytes. Experimental activities have shown that TWA on the ECG is a manifestation of an underlying alternation of long and short action potential durations (APDs), the so called APD-alternans, of cardiac myocytes in the myocardium. Understanding the mechanism of APDs-alternans is the first step for preventing them to occur. In order to investigate these mechanisms it’s very important to understand that the biological systems are complex systems and their macroscopic properties arise from the nonlinear interactions among the parts. The whole is greater than the sum of the parts, and it cannot be understood only by studying the single parts. In this sense the heart is a complex nonlinear system and its way of working follows nonlinear dynamics; alternans also, they are a manifestation of a phenomenon typical in nonlinear dynamical systems, called “period-dubling bifurcation”. Over the past decade, it has been demonstrated that electrical alternans in cardiac tissue is an important marker for the development of ventricular fibrillation and a significant predictor for mortality. It has been observed that acute exposure to low concentration of calcium does not decrease the magnitude of alternans and sustained ventricular Fibrillation (VF) is still easily induced under these condition. However with prolonged exposure to low concentration of calcium, alternans disappears, but VF is still inducible. This work is based on this observation and tries to make it clearer. The aim of this thesis is investigate the effect of hypocalcemia spatial alternans and VF doing experiments with canine hearts and perfusing them with a solution with physiological ionic concentration and with a solution with low calcium concentration (hypocalcemia); in order to investigate the so called memory effect, the experimental activity was modified during the way. The experiments were performed with the optical mapping technique, using voltage-sensitive dye, and a custom made Java code was used in post-processing. Finding the Nolasco and Dahlen’s criterion [8] inadequate for the prediction of alternans, and takin into account the experimental results, another criterion, which consider the memory effect, has been implemented. The implementation of this criterion could be the first step in the creation of a method, AP-based, discriminating who is at risk if developing VF. This work is divided into four chapters: the first is a brief presentation of the physiology of the heart; the second is a review of the major theories and discovers in the study of cardiac dynamics; the third chapter presents an overview on the experimental activity and the optical mapping technique; the forth chapter contains the presentation of the results and the conclusions.

Ruolo dell'elettrocardiogramma standard nella stratificazione prognostica della cardiomiopatia ipertrofica. Studio multicentrico

Lo scopo di questo studio è di valutare il significato prognostico dell'elettrocardiogramma standard in un'ampia casistica di pazienti affetti da cardiomiopatia ipertrofica. In questo studio multicentrico sono stati considerati 841 pazienti con cardiomiopatia ipertrofica (66% uomini, età media 48±17 anni) per un follow-up di 7.1±7.1 anni, per ognuno è stato analizzato il primo elettrocardiogramma disponibile. I risultati hanno dimostrato come fattori indipendentemente correlati a morte cardiaca improvvisa la sincope inspiegata (p 0.004), il sopraslivellamento del tratto ST e/o la presenza di onde T positive giganti (p 0.048), la durata del QRS >= 120 ms (p 0.017). Sono stati costruiti due modelli per predire il rischio di morte improvvisa: il primo basato sui fattori di rischio universalmente riconosciuti (spessore parietale >= 30 mm, tachicardie ventricolari non sostenute all'ECG Holter 24 ore, sincope e storia familiare di morte improvvisa) e il secondo con l'aggiunta delle variabili sopraslivellamento del tratto ST/onde T positive giganti e durata del QRS >= 120 ms. Entrambi i modelli stratificano i pazienti in base al numero dei fattori di rischio, ma il secondo modello risulta avere un valore predittivo maggiore (chi-square da 12 a 22, p 0.002). In conclusione nella cardiomiopatia ipertrofica l'elettrocardiogramma standard risulta avere un valore prognostico e migliora l'attuale modello di stratificazione per il rischio di morte improvvisa.

Regulation of wake-sleep states and state-dependent cardiovascular function in diet-induced obesity rats

Obesity often predisposes to coronary heart disease, heart failure, and sudden death. Also, several studies suggest a reciprocal enhancing interaction between obesity and sleep curtailment. Aim of the present study was to go deeper in the understanding of sleep and cardiovascular regulation in an animal model of diet-induced obesity (DIO). According to this, Wake-Sleep (W-S) regulation, and W-S dependent regulation of cardiovascular and metabolic/thermoregulatory function was studied in DIO rats, under normal laboratory conditions and during sleep deprivation and the following recovery period, enhancing either wake or sleep, respectively. After 8 weeks of the delivery of a hypercaloric (HC) diet, treated animals were heavier than those fed a normocaloric (NC) diet (NC: 441 ±17g; HC: 557±17g). HC rats slept more than NC ones during the activity period (Dark) of the normal 12h:12h light-dark (LD) cycle (Wake: 67.3±1.2% and 57.2 ±1.6%; NREM sleep (NREMS): 26.8±1.0% and 34.0±1.4%; REM sleep (REMS): 5.7±0. 6% and 8.6±0.7%; for NC and HC, respectively; p<0.05 for all). HC rats were hypertensive throughout the W-S states, as shown by the mean arterial blood pressure values across the 24-h period (Wake: 90.0±5.3 and 97.3±1.3; NREMS: 85.1±5.5 and 92.2±1.2; REMS: 87.2±4.5 and 96.5±1.1, mmHg for NC and HC, respectively; p<0.05 for all). Also, HC rats appeared to be slightly bradycardic compared to NC ones (Wake: 359.8±9.3 and 352.4±7.7; NREMS: 332.5±10.1 and 328.9±5.4; REMS: 338.5±9.3 and 334.4±5.8; bpm for NC and HC, respectively; p<0.05 for Wake). In HC animals, sleep regulation was not apparently altered during the sleep rebound observed in the recovery period following sleep deprivation, although REMS rebound appeared to be quicker in NC animals. In conclusion, these results indicate that in the rat obesity interfere with W-S and cardiovascular regulation and that DIO rats are suitable for further studies aimed at a better understanding of obesity comorbidities.

La cardiomiopatia aritmogena come causa di scompenso cardiaco e trapianto di cuore

Scopo dello studio: la cardiomiopatia aritmogena (CA) è conosciuta come causa di morte improvvisa, la sua relazione con lo scompenso cardiaco (SC) è stata scarsamente indagata. Scopo dello studio è la definizione della prevalenza e incidenza dello SC, nonché della fisiopatologia e delle basi morfologiche che conducono i pazienti con CA a SC e trapianto di cuore. Metodi: abbiamo analizzato retrospettivamente 64 pazienti con diagnosi di CA e confrontato i dati clinici e strumentali dei pazienti con e senza SC (NYHA III-IV). Abbiamo analizzato i cuori espiantati dei pazienti sottoposti a trapianto presso i centri di Bologna e Padova. Risultati: la prevalenza dello SC alla prima osservazione era del 14% e l’incidenza del 2,3% anno-persona. Sedici pazienti (23%) sono stati sottoposti a trapianto. I pazienti con SC erano più giovani all’esordio dei sintomi (46±16 versus 37±12 anni, p=0.04); il ventricolo destro (VD) era più dilatato e ipocinetico all’ecocardiogramma (RVOT 41±6 versus 37±7 mm, p=0.03; diametro telediastolico VD 38±11 versus 28±8 mm, p=0.0001; frazione di accorciamento 23%±7 versus 32%±11, p= 0.002). Il ventricolo sinistro (VS) era lievemente più dilatato (75±29 ml/m2 versus 60±19, p= 0.0017) e globalmente più ipocinetico (frazione di eiezione = 35%±14 versus 57%±12, p= 0.001). Il profilo emodinamico dei pazienti sottoposti a trapianto era caratterizzato da un basso indice cardiaco (1.8±0.2 l/min/m2) con pressione capillare e polmonare tendenzialmente normale (12±8 mmHg e 26±10 mmHg). L’analisi dettagliata dei 36 cuori dei pazienti trapiantati ha mostrato sostituzione fibro-adiposa transmurale nel VD e aree di fibrosi nel VS. Conclusioni: Nella CA lo SC può essere l’unico sintomo alla presentazione e condurre a trapianto un rilevante sottogruppo di pazienti. Chi sviluppa SC è più giovane, ha un interessamento del VD più severo accanto a un costante interessamento del VS, solo lievemente dilatato e ipocinetico, con sostituzione prevalentemente fibrosa.

Studio delle citochine nella distrofia muscolare di Emery-Dreifuss: Possibili marker patogenetici e bersagli di cura della malattia

La distrofia muscolare di Emery-Dreifuss (EDMD) è una miopatia degenerativa ereditaria caratterizzata da debolezza e atrofia dei muscoli senza coinvolgimento del sistema nervoso. Individui EDMD presentano, inoltre, cardiomiopatia con difetto di conduzione che provoca rischio di morte improvvisa. Diversi studi evidenziano un coinvolgimento di citochine in diverse distrofie muscolari causanti infiammazione cronica, riassorbimento osseo, necrosi cellulare. Abbiamo effettuato una valutazione simultanea della concentrazione di citochine, chemochine, fattori di crescita, presenti nel siero di un gruppo di 25 pazienti EDMD. L’analisi effettuata ha evidenziato un aumento di citochine quali IL-17, TGFβ2, INF-γ e del TGFβ1. Inoltre, una riduzione del fattore di crescita VEGF e della chemochina RANTES è stata rilevata nel siero dei pazienti EDMD rispetto ai pazienti controllo. Ulteriori analisi effettuate tramite saggio ELISA hanno evidenziato un aumento dei livelli di TGFβ2 e IL-6 nel terreno di coltura di fibroblasti EDMD2. Per testare l’effetto nei muscoli, di citochine alterate, abbiamo utilizzato terreno condizionante di fibroblasti EDMD per differenziare mioblasti murini C2C12. Una riduzione del grado di differenziamento è stata osservata nei mioblasti condizionati con terreno EDMD. Trattando queste cellule con anticorpi neutralizzanti contro TGFβ2 e IL-6 si è avuto un miglioramento del grado di differenziamento. In C2C12 che esprimevano la mutazione H222P del gene Lmna,non sono state osservate alterazioni di citochine e benefici di anticorpi neutralizzanti. I dati mostrano un effetto patogenetico delle citochine alterate come osservato in fibroblasti e siero di pazienti, suggerendo un effetto sul tessuto fibrotico di muscoli EDMD. Un effetto intrinseco alla mutazione della lamina A è stato rilevato sul espressione di caveolina 3 in mioblasti differenziati EDMD. I risultati si aggiungono a dati forniti sulla patogenesi dell' EDMD confermando che fattori intrinseci ed estrinseci contribuiscono alla malattia. Utilizzo di anticorpi neutralizzanti specifici contro fattori estrinseci potrebbe rappresentare un approccio terapeutico come mostrato in questo studio.